BU applied for COBRE funding in the first round of applications in the Spring of 2000 (awarded in September of 2000). COBRE funding was used to establish an Administrative Core; the following three Research Cores: 1) Transgenic Mouse and Knockout Core (TMKC), Genomics and Bioinformatics Core (GBC), and Microscopy and Bioimaging Core (MBC); and five Research Projects (Events Regulating the Balance Between Resistance and Infection, Genetic Models of Human Dementias, Molecular Genetics of Ion Channels, Regulation of MAPK and NF-kB Activity and Downstream Signaling, and Mechanisms of Cellular Injury and Transformation). Each research project is directed by a senior Faculty Leader-Mentor, and comprised of three to five Sub-Projects headed by Junior Faculty Investigators. The Core Facilities are typically headed by a tenure-track Faculty Leader and directed on a day-to-day basis by a research-track Faculty Director. With the exception of some staffing to be completed in the near future, all Core Facilities have been fully implemented in the first one and a half years of the COBRE award. The supplemental funding application is being submitted for the purpose of purchasing additional large equipment items for the Core Facilities. Specifically, it is proposed to: 1) enhance the functionality of the TMKC by significantly upgrading an existing Histopathology Facility; 2) expand the operation of the GBC by incorporating the technology of expression profiling using spotted cDNA arrays; and 3) to upgrade the MBC through the acquisition of versatile light microscopy and digital electron microscopy capabilities. These upgrades are necessitated by the rapidly expanding use of the COBRE Core Facilities.